HuagongsheHuagongshe Chemie-Druckbericht · Nur für Forschungszwecke
Diflunisal
DIFLUSINAL · 5-(2,4-Difluorophenyl)-2-hydroxybenzoic acid · 2',4'-Difluoro-4-hydroxy-[1,1'-biphenyl]-3-carboxylic acid · mk647 · Adomal · MK 647 · Dolisal · Dolobid
Identifikatoren & physikalische Daten
| CAS No. | 22494-42-4 |
|---|---|
| Summenformel | C13H8F2O3 |
| Durchschnittliche Molmasse | 250,2 g/mol |
| Monoisotopische Masse | 250,04415056 g/mol |
| SMILES | O=C(O)c1cc(-c2ccc(F)cc2F)ccc1O |
| InChIKey | HUPFGZXOMWLGNK-UHFFFAOYSA-N |
| PubChem CID | 3059 |
| ChEMBL | CHEMBL898 |
| ChEBI | CHEBI:39669 |
| EC No. | 245-034-9 |
| DTXSID | DTXSID5022932 |
| Lokaler Name | Diflunisal |
Chemische & physikalische Eigenschaften
| XLogP | 4,4 |
|---|---|
| Polarare Oberfläche (TPSA) | 57,5 |
| H-Brücken-Donoren | 2 |
| H-Brücken-Akzeptoren | 5 |
| Frei drehbare Bindungen | 2 |
| Schwere Atome | 18 |
| Formalladung | 0 |
| Komplexität | 311 |
| Arzneimittel | DEA NFLIS-Drug Category -> AnalgesicsPharmaceuticals -> Musculo-skeletal system -> Anti-inflammatory and antirheumatic productsPharmaceuticals -> Listed in ZINC15 |
| LogP (Verteilungskoeffizient) | 4.7 |
| Löslichkeit | Practically insoluble (14.5 mg/L) at neutral or acidic pH.7.11e-02 g/LPractically insoluble in water, soluble in ethanol (96 per cent). It dissolves in dilute solutions of alkali hydroxides.6.186mg/L(24.99 ºC) |
| Human Drugs | Breast FeedingLactationMilk, HumanAnalgesic AgentsAnti-inflammatory Agents, NonsteroidalFDA approved drugs -> Active ingredientEMA approved medicines: Human medicine |
| Schmelzpunkt | 210-211210 - 221 °C207-209C |
| Physical Description | Solid |
| Dissociation Constants | 3.3 |
| Collision Cross Section | 154.55 Ų [M+Na]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards] |
| Siedepunkt | 386.9±42.0 °C(Predicted) |
| Dichte | 1.3505 (estimate) |
| Lagerbedingungen | Keep in dark place,Sealed in dry,Room Temperature |
| pKa (Säurekonstante) | pKa 3.3 (H2O I=0.1) (Uncertain) |
| Aggregatzustand | Solid |
| Farbe | White |
| Hauptanwendungen | forensics and toxicologypharmaceutical (small molecule) |
| InChI | InChI=1S/C13H8F2O3/c14-8-2-3-9(11(15)6-8)7-1-4-12(16)10(5-7)13(17)18/h1-6,16H,(H,17,18) |
| InChIKey | HUPFGZXOMWLGNK-UHFFFAOYSA-N |
| SMILES | C1(C2=CC=C(F)C=C2F)=CC=C(O)C(C(O)=O)=C1 |
| CAS Datenbank | 22494-42-4(CAS DataBase Reference) |
| NIST chemische Informationen | Diflunisal(22494-42-4) |
Sicherheit & Vorschriften
| GHS-Einstufung | WarningH302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]P203, P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P318, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 42 reports by companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| Regulatorische Informationen | Hazard Traits - Developmental ToxicityReproductive Toxicity |
| Weitere Sicherheitsinformationen | IMAP assessments - [1,1'-Biphenyl]-3-carboxylic acid, 2',4'-difluoro-4-hydroxy-: Human health tier I assessment |
| Hazard Classes and Categories | Acute Tox. 4 (100%) |
| Treatment | In the event of overdosage, the stomach should be emptied by inducing vomiting or by gastric lavage, and the patient carefully observed and given symptomatic and supportive treatment. Because of the high degree of protein binding, hemodialysis may not be effective. (L1712) |
| Hepatotoxicity | Diflunisal therapy is reported to be associated with a low rate of asymptomatic and transient serum aminotransferase elevations, which may resolve even with drug continuation. Marked aminotransferase elevations (>3 fold elevated) occur rarely. Clinically apparent liver injury with jaundice from diflunisal is uncommononly case reports have been published. The clinical and histologic features of diflunisal hepatotoxicity, however, are distinct and resemble an immunoallergic hepatitis, which is quite different from the liver injury that occurs with aspirin or other salicylates (Case 1). The latency to onset ranges from 1 to 4 weeks and the pattern of enzyme elevations is typically cholestatic, but can also be mixed. Most patients have immunoallergic manifestations such as rash, fever and arthralgiaseosinophilia or atypical lymphocytosis are also common. A history of aspirin allergy has not been reported among cases with allergic reactions to diflunisal. Diflunisal is not a commonly used drug and is not mentioned in large case series on drug induced liver injury or acute liver failure. |
| Expositionspfade | Rapidly and completely absorbed following oral administration, with a bioavailability of 80-90%. Peak plasma concentrations are achieved 2 - 3 hours following oral administration. |
| Toxizitätsübersicht | The precise mechanism of the analgesic and anti-inflammatory actions of diflunisal is not known. Diflunisal is a prostaglandin synthetase inhibitor. In animals, prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain. Since prostaglandins are known to be among the mediators of pain and inflammation, the mode of action of diflunisal may be due to a decrease of prostaglandins in peripheral tissues. |
| Signs and Symptoms | Symptoms of overdose include coma, tachycardia, stupor, and vomiting. |
| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
| Drug Induced Liver Injury | Drug Induced Liver Injury Rank (DILIrank 2.0)DiflunisalvMost-DILI-concern8Warnings & precautionsDOI:10.1016/j.drudis.2016.02.015 |
| Effects During Pregnancy and Lactation | ◉ Summary of Use during Lactation |
| Toxicity Data | LD50: 392 mg/kg (Oral, Rat) (A308) LD50: 439 mg/kg (Oral, Mouse) (A308) LD50: 603 mg/kg (Oral, Rabbit) (A308) |
| Wassergefährdungsklasse (WGK) | 3 |
| Zollcode | 2918290000 |
| RTECS-Nr. | DV2030000 |
| R-Sätze (R) | 22-36/37/38-63 |
| Toxizität | LD50 orally in female mice: 439 mg/kg (Stone) |
| Gefahrensymbole | Xn,Xi |
| hazard_note | Irritant |
| Sicherheitshinweise (S) | 22-26-36 |
| Lagerklasse | 11 - Combustible Solids |
| Gefahrenklasse | Acute Tox. 4 OralEye Irrit. 2Repr. 2Skin Irrit. 2STOT SE 3 |
Anwendungen & Verwendung
Beschreibung
Diflunisal is more potent than aspirin but produces fewer side effects and has a biological half-life three to four times greater than that of aspirin. It is rapidly and completely absorbed on oral administration, with peak plasma levels being achieved within 2 to 3 hours of administration. It is highly bound (99%) to plasma proteins after absorption. Its elimination half-life is 8 to 12 hours, and it is excreted into urine primarily as glucuronide conjugates. The most frequently reported side effects include disturbances of the GI system (e.g., nausea, dyspepsia, and diarrhea), dermatological reactions, and CNS effects (e.g., dizziness and headache).
Verwenden
As a prostaglandin synthetase inhibitor, diflunisal exhibits analgesic, fever-reducing, and anti-inflammatory action. It is used for long- and short-lasting symptomatic relief of low to moderate pain in osteoarthritis and rheumatoid arthritis.